Three approaches to an understanding of the molecular basis of changes in gene expression during differentiation are proposed: (1) The isolation and determination of the sequence of the cDNA and the complete genes (including flanking regions) for the specific proteins of the pancreas including insulin (B cells), glucagon (A cells) and several prominent exocrine proteins (acinar cells). These DNA sequences will be used to detect changes in pancreas specific transcription during development and other regulatory transitions and in B cell diabetogenesis. They will also be used to detect and isolated the putative controlling macromolecules involved in the differentiative transition. (2) Detection and characterization of early embryonic precursor (stem?) cells and determination of developmental lineage. (3) Characterization of the mesenchymal-epithelial cell interactions required for the normal pattern of differentiation in pancreatic organogenesis.